Oncogenes, those DNA sequences that have been selected by conferring a growth advantage to cells due to alteration in sequence or aberrant transcriptional regulation, were originally identified as retroviral transduced cellular genes. We have previously isolated a defective provirus related to FeLV which transduced myc from a cat T-cell lymphoma. Two questions can be addressed regarding the molecular basis of transformation by this FeLV-myc provirus: (1) Are their alteractions in the v-myc portion of the FeLV-myc provirus that confer transforming potential to the provirus? (2) Are their DNA sequences in this feline provirus that determine the apparent T-cell tropism of FeLV-myc provirus? These questions were first addressed by determining the nucleotide sequence of the v-myc and long terminal repeat (LTR) portion of the FeLV-myc provirus. The results show that one nucleotide substitutes in exon III of v-myc causes a loss of serine residue which is normally phosphorylated in chicken c-myc to exert a transforming effect is being tested. To precisely quantitate the promotor strength of the FeLV-myc LTR and measure its activity in fibroblast, B-cells and T-cells, a chlorampherical acetyl transferase assay was performed. The results show that the FeLV-myc LTR is 31 times more active in T-cells than the Rous sarcoma virus LTR. Additionally the FeLV-myc LTR is five times more active than the Gardner-Arnstein FeLV LTR on T-cells. The major difference at the DNA sequence level which accounts for T-cell tropism by FeLV-myc is a 44 bp duplication of a core enhancer. In summary, it appears that the transforming capacity of the FeLV-myc provirus is governed both at the transcriptional level and may require point mutations in the v-myc protein which when expressed in concert in T-cells results in lymphomas.